The goal of this K24 competing renewal is to allow the Candidate, Dr. Edward Nunes, to continue to devote near full time effort to his program of research on drug abuse treatment and mentorship of aspiring clinician-investigators. Dr. Nunes' overarching goals are to develop and test new treatment interventions that have the potential to significantly improve the outcome of drug use disorders, advancing them across the spectrum from efficacy to effectiveness, and to help train and foster the next generation of clinician-researchers in the field of addictions treatment. His strategy is to seek out new innovations and develop them through clinical trials, putting together teams with the relevant expertise, and always including one or more young investigators whose career he is helping develop. The Research Plan for the new funding period will focus on: 1) Testing medications for cocaine dependence, focusing on the subgroup that fails to rapidly respond to behavioral therapy; 2) Improving the effectiveness and differential therapeutics of injection naltrexone for the treatment of opioid dependence; 3) Testing the effectiveness of an interactive web-based behavioral therapy for the treatment of substance use disorders in community-based treatment programs; and 4) Further developing and testing a method for training community-based clinicians in Motivational Interviewing. During the course of the award, Dr. Nunes will serve as PI on two R01s, PI of a Node in the NIDA-funded National Drug Abuse Clinical Trials Network, and Co-Investigator-Sponsor of a Center project, Co-I on several other R01s with junior and mid-career colleagues, and primary Mentor on two K23 awards. The Career Development Plan will expand Dr. Nunes' knowledge in the areas of statistical methods and study design, and through synergistic collaborations with other investigators in areas such as brain imaging as a tool for treatment development, and technology-based treatments. Dr. Nunes' mentoring plan focuses on clinician-investigators, particularly physicians and clinical psychologists at the post-doctoral and junior faculty level. This group is important to the field, but has been a challenge to attract and retain in research careers. This research and mentoring plan has important public health significance. Substance use disorders are a major public health problem, and remain difficult to treat. Effective new treatments have been developed, but rates of failure and relapse with each of the major substance use disorders remains high, and innovative new treatment approaches are needed. Even effective treatments often fail to be adopted in community-based practice, and effectiveness research is needed to bridge this gap. Also of great public health concern is a dearth of adequately trained physician-investigators interested in careers in addictions research. Through Dr. Nunes' activities, it is hoped that the treatment of substance use disorders will improve through his research and collaborations, and his training of the next generation of clinician-investigators. PUBLIC HEALTH RELEVANCE: The goals of this patient-oriented K24 proposal are to develop and test innovative new treatments for substance use disorders, and advance them into community-based care. These goals address a critical public health need and will be attained through the applicant's programmatic line of patient-oriented research and his mentorship of trainees, junior faculty, and other mentees, such that they obtain the necessary research skills to pursue independent clinical research toward further advancing the field of addiction treatment.